Kerstin A Klotz1,2, Yusuf Sag1, Jan Schönberger1,2, Julia Jacobs1,3. 1. Department of Neuropediatrics and Muscle Disorders, Center for Pediatrics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 3. Section of Pediatric Neurology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
Abstract
OBJECTIVE: Identification of children at risk of developing epilepsy after a first unprovoked seizure can be challenging. Interictal epileptiform discharges are associated with higher risk but have limited sensitivity and specificity. High frequency oscillations (HFOs) are newer biomarkers for epileptogenesis. We prospectively evaluated the predictive value of HFOs for developing epilepsy in scalp electroencephalogram (EEG) of children after a first unprovoked seizure. METHODS: After their first seizure, 56 children were followed prospectively over 12 months and then grouped in "epilepsy" or "no epilepsy." Initial EEGs were visually analyzed for spikes, spike ripples, and ripples. Inter-group comparisons of spike-rates and HFO-rates were done by Mann-Whitney U test. Predictive values and optimal thresholds were calculated by receiver operating characteristic (ROC) curves. RESULTS: In the epilepsy group (n = 26, 46%), mean rates of ripples (0.3 vs 0.09 / minute, p < 0.0001) and spike ripples (0.6 vs 0.06 / minute, p < 0.05) were significantly higher, with no difference in spike rates (1.7 vs 3.0 / minute, p = 0.38). Of those 3 markers, ripples showed the best predictive value (area under the curve [AUC]ripples = 0.88). The optimal threshold for ripples was calculated to be ≥ 0.125 / minute with a sensitivity of 87% and specificity of 85%. Ripple rates were negatively correlated to days passing before epilepsy-diagnosis (R = -0.59, p < 0.0001) and time to a second seizure (R = -0.64, 95% confidence interval [CI] = -0.77 to 0.43, p < 0.0001). INTERPRETATION: We could show that in a cohort of children with a first unprovoked seizure, ripples predict the development of epilepsy better than spikes or spike ripples and might be useful biomarkers in the estimation of prognosis and question of treatment. ANN NEUROL 2021;89:134-142.
OBJECTIVE: Identification of children at risk of developing epilepsy after a first unprovoked seizure can be challenging. Interictal epileptiform discharges are associated with higher risk but have limited sensitivity and specificity. High frequency oscillations (HFOs) are newer biomarkers for epileptogenesis. We prospectively evaluated the predictive value of HFOs for developing epilepsy in scalp electroencephalogram (EEG) of children after a first unprovoked seizure. METHODS: After their first seizure, 56 children were followed prospectively over 12 months and then grouped in "epilepsy" or "no epilepsy." Initial EEGs were visually analyzed for spikes, spike ripples, and ripples. Inter-group comparisons of spike-rates and HFO-rates were done by Mann-Whitney U test. Predictive values and optimal thresholds were calculated by receiver operating characteristic (ROC) curves. RESULTS: In the epilepsy group (n = 26, 46%), mean rates of ripples (0.3 vs 0.09 / minute, p < 0.0001) and spike ripples (0.6 vs 0.06 / minute, p < 0.05) were significantly higher, with no difference in spike rates (1.7 vs 3.0 / minute, p = 0.38). Of those 3 markers, ripples showed the best predictive value (area under the curve [AUC]ripples = 0.88). The optimal threshold for ripples was calculated to be ≥ 0.125 / minute with a sensitivity of 87% and specificity of 85%. Ripple rates were negatively correlated to days passing before epilepsy-diagnosis (R = -0.59, p < 0.0001) and time to a second seizure (R = -0.64, 95% confidence interval [CI] = -0.77 to 0.43, p < 0.0001). INTERPRETATION: We could show that in a cohort of children with a first unprovoked seizure, ripples predict the development of epilepsy better than spikes or spike ripples and might be useful biomarkers in the estimation of prognosis and question of treatment. ANN NEUROL 2021;89:134-142.
Authors: Jan Schönberger; Anja Knopf; Kerstin Alexandra Klotz; Matthias Dümpelmann; Andreas Schulze-Bonhage; Julia Jacobs Journal: Brain Sci Date: 2021-04-24
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